Based on excess over the requirement, methionine is the most toxic amino acid. Necrosis of the liver, kidney, pancreas spleen and increased fragility of the red blood cells are evidence in young animals consuming excess methionine whereas consumption of similar levels are not damaging in the adult. Our work indicates that metabolism of the methionine methyl group is involved in the tissue damage. Current evidence suggests that a metabolite of methionine catabolism by a pathway that does not involve the formation of S-adenosylmethionine is involved in the toxicity of methionine. Our thesis is that metabolism of methionine via this pathway involves its transamination to the keto acid, decarboxylation of the keto acid to methylthiopropionate (MTP) and conversion of the MTP to methylmercaptan and a propionate-like compound. Additionally, we postulate that methylmercaptan is broken down via hydrogen sulfide before it is converted to sulfate and carbon dioxide. We have shown that keto acid of methionine is an intermediate in this pathway and these experiments are designed to test whether MTP is an intermediate of methionine degradation by using trapping pools of MTP to determine if label from methionine is recovered in it. Identification of MTP as an intermediate will be verified by a combination of ion exchange chromatography, thin layer chromatography and gas chromatography. Because the metabolism of the keto acid of methionine in a liver homogenate system yields volatile sulfur, the identity of the volatile sulfur compounds will be investigated by a combination of gas chromatography and mass spectrometry. Similar experiments will be conducted with samples of monkey and human fetal liver to determine if the pathways of methionine degradation discovered in the rat also exist in primates. The control of methionine degradation will be investigated by comparing variations in the activity of cystathionine synthase and methionine decarboxylase (alpha-keto-gamma-methiolbutyrate yields methylthiopropionate plus CO2) with the capacity of the liver homogenate system, a liver free cell system or intact animals to oxidize methionine.